Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression

Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients’ T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. Conclusions: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression

Diagnosis and treatment of cervical cancer during pregnancy

CONTEXT AND OBJECTIVE: One third of all cervical carcinomas occur during the reproductive period. Cervical carcinoma is the second greatest cause of death due to cancer during this phase. The estimated frequency of cervical cancer during pregnancy is one case for every 1,000 to 5,000 pregnancies. The aim here was to provide information about the difficulties in diagnosing and managing cervical neoplasia during pregnancy. MATERIALS: A systematic review of the literature was undertaken through the PubMed, Cochrane, Excerpta Medica (Embase), Literatura Latino Americana e do Caribe em Ciências da Saúde (Lilacs) and Scientific Electronic Library Online (SciELO) databases, using the following words: pregnancy, cervical cancer, diagnosis and management. RESULTS: There was a consensus in the literature regarding diagnosis of cervical carcinoma and management of preneoplastic lesions during pregnancy. However, for management of invasive carcinoma, there was great divergence regarding the gestational age taken as the limit for observation rather than immediate treatment. CONCLUSION: All patients with cytological abnormalities should undergo colposcopy, which will indicate and guide biopsy. Conization is reserved for patients with suspected invasion. High-grade lesions should be monitored during pregnancy and reevaluated after delivery. In cases of invasive carcinoma detected up to the 12th week of pregnancy, patient treatment is prioritized. Regarding diagnoses made during the second trimester, fetal pulmonary maturity can be awaited, and the use of chemotherapy to stabilize the disease until the time of delivery appears to be viable.CONTEXTO E OBJETIVO: Um terço dos carcinomas de colo ocorrem no período reprodutivo, sendo que esta é a segunda causa de morte por câncer nessa fase. A freqüência estimada do carcinoma de colo uterino na gravidez é de um caso para cada 1.000 a 5.000 gestações. O objetivo foi informar sobre as dificuldades frente ao diagnóstico e manejo da neoplasia cervical durante a gravidez. MATERIAIS E MÉTODOS: Revisão sistemática da literatura foi realizada no PubMed, Cochrane, Excerpta Medica (Embase), Literatura Latino Americana e do Caribe em Ciências da Saúde (Lilacs) and Scientific Electronic Library Online (SciELO), usando as seguintes palavras: gestação, câncer cervical, diagnóstico e manejo. RESULTADOS: A literatura apresenta consenso quanto ao diagnóstico do carcinoma cervical e a conduta das lesões pré-neoplásicas durante a gestação. No manejo do carcinoma invasor há grande divergência quanto à idade gestacional considerada como limite para a adoção da observação em vez do tratamento imediato. CONCLUSÃO: Toda paciente com citologia alterada deve realizar colposcopia, a qual indicará e a biópsia. A conização é reservada para pacientes com suspeita de invasão. As lesões de alto grau devem ser acompanhadas durante a gestação e reavaliadas após o parto. Em casos de carcinoma invasor em gestantes com até 12 semanas o tratamento da paciente é priorizado. Nos diagnósticos ocorridos no segundo trimestre, pode-se aguardar a maturidade pulmonar fetal e o uso da quimioterapia para estabilizar a doença até o momento do parto parece ser viável